The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates.
Cell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells. These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy. The intracellular growth of Salmonella enterica occurs in a membra...
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2012-01-01
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doaj-a511cd1048664a6690244cc63c80a22f2020-11-25T01:50:11ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0186e100274310.1371/journal.ppat.1002743The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates.Francisco S MesquitaMair ThomasMartin SachseAntónio J M SantosRita FigueiraDavid W HoldenCell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells. These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy. The intracellular growth of Salmonella enterica occurs in a membranous compartment, the Salmonella-containing vacuole (SCV), and is dependent on effectors translocated to the host cytoplasm by the Salmonella pathogenicity island-2 (SPI-2) encoded type III secretion system (T3SS). Here, we show that bacterial replication is accompanied by the formation of ubiquitinated structures in infected cells. Analysis of bacterial strains carrying mutations in genes encoding SPI-2 T3SS effectors revealed that in epithelial cells, formation of these ubiquitinated structures is dependent on SPI-2 T3SS effector translocation, but is counteracted by the SPI-2 T3SS deubiquitinase SseL. In macrophages, both SPI-2 T3SS-dependent aggregates and aggresome-like induced structures (ALIS) are deubiquitinated by SseL. In the absence of SseL activity, ubiquitinated structures are recognized by the autophagy receptor p62, which recruits LC3 and targets them for autophagic degradation. We found that SseL activity lowers autophagic flux and favours intracellular Salmonella replication. Our data therefore show that there is a host selective autophagy response to intracellular Salmonella infection, which is counteracted by the deubiquitinase SseL.http://europepmc.org/articles/PMC3375275?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francisco S Mesquita Mair Thomas Martin Sachse António J M Santos Rita Figueira David W Holden |
spellingShingle |
Francisco S Mesquita Mair Thomas Martin Sachse António J M Santos Rita Figueira David W Holden The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. PLoS Pathogens |
author_facet |
Francisco S Mesquita Mair Thomas Martin Sachse António J M Santos Rita Figueira David W Holden |
author_sort |
Francisco S Mesquita |
title |
The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. |
title_short |
The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. |
title_full |
The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. |
title_fullStr |
The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. |
title_full_unstemmed |
The Salmonella deubiquitinase SseL inhibits selective autophagy of cytosolic aggregates. |
title_sort |
salmonella deubiquitinase ssel inhibits selective autophagy of cytosolic aggregates. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2012-01-01 |
description |
Cell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells. These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy. The intracellular growth of Salmonella enterica occurs in a membranous compartment, the Salmonella-containing vacuole (SCV), and is dependent on effectors translocated to the host cytoplasm by the Salmonella pathogenicity island-2 (SPI-2) encoded type III secretion system (T3SS). Here, we show that bacterial replication is accompanied by the formation of ubiquitinated structures in infected cells. Analysis of bacterial strains carrying mutations in genes encoding SPI-2 T3SS effectors revealed that in epithelial cells, formation of these ubiquitinated structures is dependent on SPI-2 T3SS effector translocation, but is counteracted by the SPI-2 T3SS deubiquitinase SseL. In macrophages, both SPI-2 T3SS-dependent aggregates and aggresome-like induced structures (ALIS) are deubiquitinated by SseL. In the absence of SseL activity, ubiquitinated structures are recognized by the autophagy receptor p62, which recruits LC3 and targets them for autophagic degradation. We found that SseL activity lowers autophagic flux and favours intracellular Salmonella replication. Our data therefore show that there is a host selective autophagy response to intracellular Salmonella infection, which is counteracted by the deubiquitinase SseL. |
url |
http://europepmc.org/articles/PMC3375275?pdf=render |
work_keys_str_mv |
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